Réponses immunitaires au vaccin contre le virus SARS-CoV-2 et infections perthérapeutiques chez des personnes atteintes de sclérose en plaques (SEP) traitées par ocrélizumab (OCR)

Référent isabelle.lawrence@potentieldaction.com (I. Lawrence). Introduction Il a été rapporté des taux d'anticorps atténués et une réponse cellulaire T robuste après vaccination anti-SARS-CoV-2 (CoV) chez des patients atteints de SEP traités par OCR. Ces réponses immunitaires et leur lien avec la protection clinique sont mal compris. Objectifs Étudier l'effet d'OCR sur la production d'anticorps et de lymphocytes T en réponse au vaccin anti-CoV. Caractériser cliniquement les infections COVID-19 perthérapeutiques chez les personnes atteintes de SEP. Méthodes Les patients de 3 études de phase IIIb évaluant OCR, ayant souhaité recevoir un vaccin contre le SARS-CoV-2, ont participé à une évaluation exploratoire facultative. Les anticorps ont été dosés par électrochimioluminescence (Elecsys®) et les cellules T spécifiques contre 4 pools peptidiques de la protéine spike détectées par ELISpot Interferon-gamma (ImmunoSpot). Une infection perthérapeutique est définie comme une infection COVID-19 suspectée ou confirmée en laboratoire, survenant ≥ 14 jours après la primovaccination. Résultats Les échantillons de 111 patients (la plupart sous OCR ≥ 2 ans) ont été recueillis jusqu'en 09/2021. Au total, 72,1 % SEP récurrente-rémittente, 15,3 % SEP progressive-secondaire, 12,6 % SEP primaire-progressive. En moyenne (ET), 78,5 (41,4) jours séparaient la 1re dose de vaccin et la dernière perfusion d'OCR. Au total, 94/111 patients ont reçu un vaccin à ARNm, 15 un adénoviral. Une réponse à anticorps a été détectée chez 22/103 (21 %) patients et à lymphocytes T chez 83/95 (87 %). Quatre cas d'infection rapportés. Discussion Des analyses élargies (∼450 patients, jusqu'en 03/2022) seront présentées: réponses longitudinales, données après rappel vaccinal, différences entre les plateformes vaccinales, évaluation des facteurs susceptibles d'affecter les réponses immunitaires. Les corrélations entre le niveau des réponses immunitaires et le diagnostic et la sévérité de l'infection perthérapeutique seront explorées. Conclusion La proportion des personnes atteintes de SEP traitées par OCR répondant à une vaccination par la présence d'anticorps et de lymphocytes T était conforme aux données publiées.

Risk Factors for Infection and Health Impacts of the Coronavirus Disease 2019 (COVID-19) Pandemic in People With Autoimmune Diseases.

BACKGROUND: People with autoimmune or inflammatory conditions taking immunomodulatory/suppressive medications may have higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences. METHODS: We included participants with autoimmune or inflammatory conditions followed by specialists at Johns Hopkins. Participants completed periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. We assessed whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterized pandemic-associated changes to care and mental health. RESULTS: In total, 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medications) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in models incorporating behavior and other potential confounders (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95% CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95% CI: 1.24, 2.28), and kidney disease (OR: 1.76; 95% CI: 1.04, 2.97) were associated with higher odds of COVID-19. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions therein, which disproportionately affected individuals experiencing changes to employment or income. CONCLUSIONS: Glucocorticoid exposure may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.

Discordant humoral and T cell immune responses to SARS-CoV-2 vaccination in people with multiple sclerosis on anti-CD20 therapy.

BACKGROUND: Sphingosine-1-phosphate receptor (S1P) modulators and anti-CD20 therapies impair humoral responses to SARS-CoV-2 mRNA vaccines. Relatively few studies have assessed the impact of an array of disease modifying therapies (DMTs) for multiple sclerosis (MS) on T cell immune responses to SARS-CoV-2 vaccination. METHODS: In 101 people with MS, we measured humoral responses via an immunoassay to measure IgG against the COVID-19 spike S1 glycoprotein in serum. We also measured T cell responses using FluoroSpot assay for interferon gamma (IFN-γ) (Mabtech, Sweden) using cryopreserved rested PBMCs and then incubated in cRPMI with 1µg/ml of pooled peptides spanning the entire spike glycoprotein (Genscript, 2 pools; 158 peptides each). Plates were read on an AID iSpot Spectrum to determine the number of spot forming cells (SFC)/106 PBMCs. We tested for differences in immune responses across DMTs using linear models. FINDINGS: Humoral responses were detected in 22/39 (56.4%) participants on anti-CD20 and in 59/63 (93.6%) participants on no or other DMTs. In a subset (n=88; 87%), T cell responses were detected in 76/88 (86%), including 32/33 (96.9%) participants on anti-CD20 therapies. Anti-CD20 therapies were associated with an increase in IFN-γ SFC counts relative to those on no DMT or other DMTs (for anti-CD20 vs. no DMT: 425.9% higher [95%CI: 109.6%, 1206.6%] higher; p<0.001; for anti-CD20 vs. other DMTs: 289.6% [95%CI: 85.9%, 716.6%] higher; p<0.001). INTERPRETATION: We identified a robust T cell response in individuals on anti-CD20 therapies despite a reduced humoral response to SARS-CoV-2 vaccination. Follow up studies are needed to determine if this translates to protection against COVID-19 infection. FUNDING: This study was funded partially by 1K01MH121582-01 from NIH/NIMH and TA-1805-31136 from the National MS Society (NMSS) to KCF and TA-1503-03465 and JF-2007-37655 from the NMSS to PB. This study was also supported through the generosity of the collective community of donors to the Johns Hopkins University School of Medicine for COVID research.